Abstract

This project aims to address the question whether the elevated levels of glutamate and other neurotransmitters that have been reported in brain following an ischemic insult are indeed important in the subsequent cascade of events leading to cell death or whether they are merely an expression of generalized energy failure. The studies will examine the temporal pattern of changes in the extracellular concentration of excitatory amino acids (EAA) and glycine following episodes of transient global ischemia in rabbits. Microdialysis will be used to obtain fine resolution measurements of regional brain tissue concentrations of these transmitter substances. The relationship between various physiological variables and pharmacological agents thought to alter neurologic outcome and the release of EEA will be analyzed. These agents will include NMDA antagonists and adenosine agonists. The results of these studies will provide a better understanding of the mechanisms of neurological injury in ischemic hypoxia and will help to resolve some of the questions regarding the therapeutic benefit of various neuroprotective agents and interventions.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS029403-02
Application #
3416206
Study Section
Neurology A Study Section (NEUA)
Project Start
1991-05-01
Project End
1995-04-30
Budget Start
1992-05-01
Budget End
1993-04-30
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Frederickson, C J; Giblin, L J; Krezel, A et al. (2006) Concentrations of extracellular free zinc (pZn)e in the central nervous system during simple anesthetization, ischemia and reperfusion. Exp Neurol 198:285-93
Mueller, Rashmi N; Deyo, Donald J; Brantley, David R et al. (2003) Lubeluzole and conditioned learning after cerebral ischemia. Exp Brain Res 152:329-34
Koinig, H; Vornik, V; Rueda, C et al. (2001) Lubeluzole inhibits accumulation of extracellular glutamate in the hippocampus during transient global cerebral ischemia. Brain Res 898:297-302
Koinig, H; Morimoto, Y; Zornow, M H (2001) The combination of lamotrigine and mild hypothermia prevents ischemia-induced increase in hippocampal glutamate. J Neurosurg Anesthesiol 13:106-12
Koinig, H; Williams, J P; Quast, M J et al. (2000) Effect of a neuronal sodium channel blocker on magnetic resonance derived indices of brain water content during global cerebral ischemia. Brain Res 887:301-8
Kwon, J Y; Bacher, A; Deyo, D J et al. (2000) Effects of pentobarbital and isoflurane on conditioned learning after transient global cerebral ischemia in rabbits. Anesthesiology 92:171-7
Kwon, J Y; Bacher, A; Deyo, D J et al. (1999) Effects of hypothermia and lamotrigine on trace-conditioned learning after global cerebral ischemia in rabbits. Exp Neurol 159:105-13
Martinez-Tica, J F; Berbarie, R; Davenport, P et al. (1999) Monitoring brain PO2, PCO2, and pH during graded levels of hypoxemia in rabbits. J Neurosurg Anesthesiol 11:260-3
Bacher, A; Wei, J; Grafe, M R et al. (1998) Serial determinations of cerebral water content by magnetic resonance imaging after an infusion of hypertonic saline. Crit Care Med 26:108-14
Bacher, A; Kwon, J Y; Zornow, M H (1998) Effects of temperature on cerebral tissue oxygen tension, carbon dioxide tension, and pH during transient global ischemia in rabbits. Anesthesiology 88:403-9

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